Molecular genetics of familial parkinsonism

Parkinson's disease (PD) is a progressive, neurodegenerative disorder associated with tremor, rigidity, bradykinesia, and postural instability. There exists a familial form of PD that is indistinguishable from the sporadic form. In addition, there exists a class of syndromes classified as parkinsonism-plus syndromes (PPS), in which parkinsonism is an essential but not the only phenotypic characteristic. The etiology of PD remains unclear. Both environmental and genetic factors contribute to the disease pathogenesis. Recent progress in the molecular genetics of parkinsonism has demonstrated that six different chromosomal regions are associated with forms of familial parkinsonism. Mutations in four candidate genes have been identified and include both point mutations and deletions. Both gain-of-function and loss-of-function mutational mechanisms have been implicated. The molecular genetic characterization has led to a new classification of PD and PPS based on the type of genetic defect. Understanding the mechanisms by which these mutations lead to disease should provide further insights into the etiology of parkinsonism.     

Classification of childhood epilepsy syndromes in newly diagnosed epilepsy: interrater agreement and reasons for disagreement

PURPOSE: The International League Against Epilepsy (ILAE) classification of the epilepsies is in increasingly widespread use. The following analysis was done to assess the interrater agreement in classifying epilepsy syndromes in children with newly diagnosed epilepsy. METHODS: In a prospective, community-based study, 613 children with newly diagnosed epilepsy were recruited. Based on information available at diagnosis or generated as part of the initial diagnostic assessment, three pediatric neurologists independently classified epilepsy syndromes. Interrater agreement was assessed with kappa. RESULTS: Interrater agreement was extremely good, with kappa scores > or = 0.80 for almost all comparisons. Relatively limited quality of the EEG and seizure information in some cases, as well as discrepancies between the two, were associated with a tendency for more disagreement. CONCLUSIONS: A high degree of interrater agreement was obtained in this study, indicating that the system for classifying syndromes can be meaningfully used in a community-based sample. Quality of the information, which is often, by necessity, less than optimal in newly diagnosed epilepsy, is a potential barrier to identification of syndromes. A substantial proportion of children were classified into relatively nonspecific syndromes. Over time, additional information may come to light to allow more precise identification of their forms of epilepsy. In an epidemiologic setting, the ILAE classification of the epilepsies can be successfully used with a high degree of reliability to classify newly diagnosed epilepsy in children.     

鼻塞对阻塞性睡眠呼吸暂停综合征发病影响的研究

目的:探讨鼻塞对阻塞性睡眠呼吸暂停综合征(OSAS)发病的影响。方法:对18例诊断为鼻塞和腭咽平面阻塞的OSAS患者,单纯行鼻腔手术改善通气,6个月后复诊。结果:12例睡眠阻塞症状缓解,其中4例效果明显;6例无效。睡眠呼吸紊乱指数(AHI)由术前的29.9±2.1降至22.8±2.7;夜间最低血氧饱和度由(75.0±2.9)％升至(83.4±2.3)％;而体重指数无明显差异。无效组与有效组的术前AHI值差异有显著性意义。结论:鼻塞是OSAS的重要致病因素,早期治疗解除鼻塞是预防OSAS发病的重要措施之一;长期鼻塞引发的OS-AS患者,早期通过鼻腔手术解除鼻塞是治疗OSAS的有效方法之一。     

慢性肾功能衰竭中医证候研究现状

中医证候规范化研究已成为当前中医界的重大课题之一，近年来，诸多医家从不同角度对慢性肾功能衰竭（CRF）的病因病机，辨证分,下候规范化进行了较深层次的探讨。由于CRF的中医证候复杂，并且呈动态变化，故应加强对其辨证分型和证候规范化的进一步研究。     

辨证治疗中风病248例临床分析

本文通过对２４８例中风病临床分型分析，以气虚血瘀证最多，占３８．３１％，其次为阴虚风动证，肝阳暴亢，风火上扰证。本组病人不论是出血性中风，还是缺血性中风，均采用中药辨证治疗基础上，口服中成药及静脉滴注活血化瘀针剂以加强活血化瘀、涤痰通络这一治疗法则，总有效率为８４．２７％，其中出血性中风和缺血性中风的总有效率分别为８６．９５％和８３．２４％，对血液流变学、脑出血患者治疗前后脑ＣＴ对照观察，认为 一     

Initial transforming event in myelodysplastic syndromes may be viral: case for cytomegalovirus

Myelodysplastic syndromes (MDS) are clonal hematopoietic disorders which begin in a pluripotential bone marrow (BM) stem cell. This early stem cell is believed to acquire a growth advantage over its neighbors as a result of an initial transforming event, the nature of which has remained obscure. In this paper, we propose that pathogens such as those belonging to the herpesvirus family of DNA viruses may play a role in the initial transformation of the stem cell. The case for cytomegalovirus (CMV) as a representative of this family of viruses is discussed at length and a molecular mechanism which may be involved in the oncogenic activity of CMV is proposed. No proof has been presented to implicate CMV directly in MDS, but circumstantial evidence which supports such a possibility is provided.     

马利兰和环磷酰胺预处理方案的非亲缘异基因骨髓移植治疗骨髓增生异常综合征

目的:评估以马利兰和环磷酰胺(Bu-CY2)为预处理方案的非亲缘异基因骨髓移植治疗骨髓增生异常综合征(MDS)的临床疗效。方法:对6例MDS患者进行非亲缘异基因骨髓移植术,以Bu-CY2为预处理方案,Bu 4 m g.k-g 1.d-1,-7 d~-4 d,CY 60 m g.k-g 1.-d 1,-3 d~-2 d。输入单个核细胞数(MNC)为3.38×108/kg(2.4×108/kg~4.6×108/kg),CD 34+细胞数5.81×106/kg(1.2×106/kg~8.5×106/kg),粒-巨噬细胞集落形成单位(CFU-GM)数2.88×105/kg(1.61×105/kg~4.56×105/kg)。以霉酚酸酯加环孢素A(C sA)和短程氨甲蝶呤(MTX)预防移植物抗宿主病,前列腺素E1脂质微球预防肝静脉阻塞病。结果:6例患者中性粒细胞≥0.5×109/L的中位时间为18 d(13~21 d),血小板≥20×109/L的中位时间为21 d(13~24 d)。经DNA短串联重复序列多态性分析和染色体检查,均为供者骨髓植活。早期死亡率为0,移植后随访时间为27个月(6~60个月)。目前实际无病生存6例,缓解期实际生存率100%。结论:以Bu-CY2为预处理方案的非亲缘异基因骨髓移植是治疗MDS的有效方法。     

范永升教授诊治系统性红斑狼疮经验

范永升教授认为系统性红斑狼疮的病因病机以肾虚为本,热毒、瘀血为标;在辨病辨证基础上,以解毒祛瘀滋肾为大法并结合西药综合治疗,取得了较好疗效。     

c-FLIP与细胞凋亡及其在骨髓增生异常综合征中的研究

部分骨髓增生异常综合征(MDS)可转化为恶性白血病,骨髓细胞凋亡异常是其主要的发病机制之一.细胞型FLIP(c-FLIP)参与了多种肿瘤的发生和发展过程,是细胞凋亡通路中一个重要的调控器,并且它具有多样的表达形式及作用机制.c-FLIP在MDS发病机制中的作用得到了广泛的关注和研究.